| General information |
| Database: | DB00956 |
| Objective: | Programmed cell death 1 (PD1) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory. PD1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma, but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued. |
| Authors: | Topalian SL, et al |
| Title: | Survival, durable tumor remission, and longterm safety in patients with advanced melanoma receiving nivolumab. |
| Journal: | J Clin Oncol. |
| Year: | 2014 |
| PMID: | 24590637 |
| Trial Design |
| Clinical Trial Id: | NCT00730639 |
| Agent: | nivolumab
|
| Target: | programmed death1
|
| Cancer Type: | melanoma |
| Cancer Subtype: | advanced melanoma |
| Therapy Type: | mono |
| Therapeutic Combination Type: | NA |
| Therapeutic Combination Content: | NA |
| Study Type: | doseescalation, cohort expansion study |
| Key Patients Feature: | Patients with melanoma arising from any primary site, including ocular, were required to have measurable disease by RECIST |
| Biomarker: | NA |
| Biomark Analysis: | NA |
| Control Group Info: | single arm |
| Treatment Info: | pts received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks |
| Primary End Point: | overall survival, longterm safety, and response duration after treatment discontinuation |
| Secondary End Point: | NA |
| Patients Number: | 107 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | 31% |
| Disease Control Rate: | 38% |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | 3.7 months (95% CI, 1.9 to 9.1 months), with 1 and 2year progression free survival rates of 36% (95% CI, 27% to 46%) and 27% (95% CI, 17% to 36%), respectively |
| Median OS A vs. C: | in nivolumabtreated patients (62% with two to five prior systemic therapies) was 16.8 months, and 1 and 2year survival rates were 62% and 43%, respectively. |
| Adverse Event(agent arm): | The most common events of any grade that occurred in patients with melanoma were fatigue (32%), rash (23%), and diarrhea (18%). Twentyfour (22%) of 107 patients with melanoma experienced grade 3 to 4 treatmentrelated adverse events. |
| Conclusions: | Overall survival following nivolumab treatment in patients with advanced treatmentrefractory melanoma compares favorably with that in literature studies of similar patient populations. Responses were durable and persisted after drug discontinuation. Longterm safety was acceptable. Ongoing randomized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma. |